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University of Michigan Peltier Results Average time courses (top) and their corresponding power spectra (bottom) for the left (blue, solid) and right (red, dashed) motor cortices for a typical subject, before and after fatigue. The time courses and their corresponding frequency content are more dissimilar after the fatigue task, with the left and right motor cortices' time courses having a correlation of 0.95 before and 0.64 after the fatigue task.The time courses and their corresponding frequency content are more dissimilar after the fatigue task, with the left and right motor cortices' time courses having a correlation of 0.95 before and 0.64 after the fatigue task. Time (seconds) Normalized amplitude amplitude Frequency (Hz) Normalized amplitude amplitude Before fatigue After fatigue

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University of Michigan Peltier Results Interhemispheric correlation in both cortices decreases after the fatigue task.Interhemispheric correlation in both cortices decreases after the fatigue task. Across all subjects, there was a 72% reduction in the number of significant mean correlations (p < 0.05) from before fatigue.Across all subjects, there was a 72% reduction in the number of significant mean correlations (p < 0.05) from before fatigue. Beforefatiguetask Afterfatiguetask Interhemispheric correlation for motor cortex voxels in four of the eight subjects before and after the fatigue task. Histogram of the mean interhemispheric correlation values over all subjects before (red) and after (blue) fatigue. Peltier et al., Brain Research, 1057:11 (2005)

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University of Michigan Peltier Asperger’s Disorder Previous study* identified resting-state “default mode” network including PCC, thought to be associated with internal focus, social awarenessPrevious study* identified resting-state “default mode” network including PCC, thought to be associated with internal focus, social awareness Subjects with Asperger’s Disorder have deficits in social interactionSubjects with Asperger’s Disorder have deficits in social interaction This work examined this network in adults with Asperger’s Disorder and control subjectsThis work examined this network in adults with Asperger’s Disorder and control subjects * Grecius et al.(2003) PNAS 100:253 Raichle et al,. (2001) PNAS 98:676

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University of Michigan Peltier Connectivity results Functional connectivity results for each group using a seed in the posterior cingulate (indicated by arrow). The average map is thresholded at 0.25 coincidence and >5 connecting voxels for viewing purposes.Functional connectivity results for each group using a seed in the posterior cingulate (indicated by arrow). The average map is thresholded at 0.25 coincidence and >5 connecting voxels for viewing purposes. Healthy controls z=+27.5z=+22.5z=+17.5z=+12.5z=+7.5 Separate controls

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University of Michigan Peltier Connectivity results Functional connectivity results for each group using a seed in the posterior cingulate (indicated by arrow). The average map is thresholded at 0.25 coincidence and >5 connecting voxels for viewing purposes.Functional connectivity results for each group using a seed in the posterior cingulate (indicated by arrow). The average map is thresholded at 0.25 coincidence and >5 connecting voxels for viewing purposes. Healthy controls z=+27.5z=+22.5z=+17.5z=+12.5z=+7.5 Subjects with Asperger’s Disorder

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University of Michigan Peltier Connectivity results T-test of group values revealed a significant difference (p < ) between the two groups.T-test of group values revealed a significant difference (p < ) between the two groups. The separate control group connectivity map was used as a reference mapThe separate control group connectivity map was used as a reference map With the current data, a threshold of 0.22 classifies Asperger’s subjects with 100% accuracy, and control subjects with 80% accuracy.With the current data, a threshold of 0.22 classifies Asperger’s subjects with 100% accuracy, and control subjects with 80% accuracy Coefficient of areal correspondence AD subjects HC subjects

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University of Michigan Peltier Monk et al., Neuroimage 47: (2009). Autism, continued Recent work has related behavioral measures of social deficits in subjects with autism to resting state functional connectivity.

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University of Michigan Peltier Summary Functional connectivity patterns associated with the PCC differentiated between controls and adults with Asperger’s DisorderFunctional connectivity patterns associated with the PCC differentiated between controls and adults with Asperger’s Disorder Functional connectivity thus may serve as a potential biomarker of Asperger’s DisorderFunctional connectivity thus may serve as a potential biomarker of Asperger’s Disorder

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University of Michigan Peltier Anesthesia The mechanism of anesthesia, a (reversible) state of profound CNS suppression, is not completely understoodThe mechanism of anesthesia, a (reversible) state of profound CNS suppression, is not completely understood Anesthesia is not a uniform entity, with different end- points of interest, including ablation of motor responses, memory function, and consciousnessAnesthesia is not a uniform entity, with different end- points of interest, including ablation of motor responses, memory function, and consciousness –Veselis. Consc Cogn 10:230 (2001) Recent studies underline a necessity to address global disconnecting effects, besides the regional suppressive effects of anesthetic agents on isolated brain structuresRecent studies underline a necessity to address global disconnecting effects, besides the regional suppressive effects of anesthetic agents on isolated brain structures –White & Alkire. Neuroimage 19:402 (2003)

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University of Michigan Peltier Objective By employing gradations of anesthetic influence, we explored the effect of anesthesia on fMRI resting-state functional connectivity of the motor networkBy employing gradations of anesthetic influence, we explored the effect of anesthesia on fMRI resting-state functional connectivity of the motor network Examined suppression and disconnection effectsExamined suppression and disconnection effects

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University of Michigan Peltier Methods Awake Deep Light 0% 1% 2% Sevoflurane concentration Time Anesthesia 6 right-handed, male volunteers were studied under three successive conditions: while breathing 0, 2.0 and 1.0% end-tidal sevoflurane (Awake, Deep, Light state, respectively).6 right-handed, male volunteers were studied under three successive conditions: while breathing 0, 2.0 and 1.0% end-tidal sevoflurane (Awake, Deep, Light state, respectively). Sevoflurane concentration was held constant for 15 min to allow for equilibration at each level, after which scans were obtained.Sevoflurane concentration was held constant for 15 min to allow for equilibration at each level, after which scans were obtained. Acquisition EPI pulse sequence was used on a 3 T Siemens Trio scanner, TR/TE/FA/FOV = 750 ms/35 ms/50°/22 cm. Ten 5 mm thick axial slices were acquired in each TR, with in-plane resolution of 3.44 mm x 3.44 mm. In each condition, 280 images were collected.EPI pulse sequence was used on a 3 T Siemens Trio scanner, TR/TE/FA/FOV = 750 ms/35 ms/50°/22 cm. Ten 5 mm thick axial slices were acquired in each TR, with in-plane resolution of 3.44 mm x 3.44 mm. In each condition, 280 images were collected. Data were acquired while volunteers were lying still, with eyes closed.Data were acquired while volunteers were lying still, with eyes closed. Simultaneous acquisition of the cardiac rhythm was done using a pulse oximeter.Simultaneous acquisition of the cardiac rhythm was done using a pulse oximeter.

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University of Michigan Peltier Results - disconnection Laterality in Light state investigated further using right and left motor seedsLaterality in Light state investigated further using right and left motor seeds Resultant functional connectivity maps show stronger response in hemisphere of seedResultant functional connectivity maps show stronger response in hemisphere of seed Slice 1 Slice 2 Slice 3 Light anesthesia

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University of Michigan Peltier Summary Sevoflurane anesthesia significantly reduces synchronized, functionally related activations throughout the hemispheresSevoflurane anesthesia significantly reduces synchronized, functionally related activations throughout the hemispheres Additionally, in comparing the awake state to that of light anesthesia, we observe a shift from bilateral to unilateral functional connectivity in the motor networkAdditionally, in comparing the awake state to that of light anesthesia, we observe a shift from bilateral to unilateral functional connectivity in the motor network This has implications for how anesthetic concentrations affect cortical activity, and for characterizing functional connectivity in brain networksThis has implications for how anesthetic concentrations affect cortical activity, and for characterizing functional connectivity in brain networks Peltier et al., NeuroReport, 16:285 (2005)

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University of Michigan Peltier Practical considerations Resting-state networks are affected by condition, preceding tasksResting-state networks are affected by condition, preceding tasks –Consider order of experiments in study Resting-state networks are relatively robust over voxel size selection, duration of scans (5-6 minutes or longer)Resting-state networks are relatively robust over voxel size selection, duration of scans (5-6 minutes or longer) –Optimize for normal fMRI considerations –Be aware of loss of degrees of freedom in single subject analysis Nuisance covariates are important to consider (residual head motion, physiological waveforms, etc)Nuisance covariates are important to consider (residual head motion, physiological waveforms, etc)

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University of Michigan Peltier Physiological noise Physiological noise can alias into band of interestPhysiological noise can alias into band of interest –Faster acquisition can help with this, but not always feasible –Acquire physiological rhythms (respiration, cardiac) for use as nuisance covariates (e.g. RETROICOR) –Can generate estimate of physiological waveforms from data itself (e.g. CompCor)